SUMMARY/ABSTRACT: OVERALL Kidney stone disease (nephrolithiasis) is a significant source of morbidity in the United States and mortality in the developing world. Development of a resource that supports a mission of cross-discipline, multi-institutional discovery is the overall goal of this P20. We intend to accomplish this by creating a Resource Development Project whose aim is to establish and validate an automated clinical registry called ReSKU (Registry for Stones of the Kidney and Ureter) that integrates with the electronic medical record (EMR) system, provides high quality clinical data for research purposes, and does not require an excessive time or cost commitment from providers to participate. Such a registry would be a cornerstone in linking clinical and translational studies in nephrolithiasis. Basic and translational research that relies on the use of human biospecimens often lacks a clinical context to identify ways in which new findings can be applied for patients. Clinical registries are the key to linking between these two worlds. In developing ReSKU, we first recognized how current registries operate and how an ideal modern registry would compare since traditional registry design and data entry are accompanied by challenges that hinder their implementation. These include labor-intensive data entry, cost of registry maintenance, patient confidentiality with meeting HIPAA requirements and human subjects research regulations, manpower for maintaining and organizing a database, concerns for how data will be stored and used, and interference with day to day clinical care. ReSKU is easy to populate via integration with existing electronic health record systems and have a low maintenance cost, all while recording accurate, detailed patient clinical information, documenting surgeon outcomes, and tracking quality of care. By leveraging the EHR, many of the challenges facing patient registries are overcome. We have utilized ReSKU at UCSF to create an infrastructure on which clinical and translational research studies have been successfully completed. This includes studies on ultrasound guidance for percutaneous surgery, contrast enhanced ultrasound as a new diagnostic imaging modality, and novel therapeutics identification for nephrolithiasis patients. These projects have been successfully in large part because ReSKU accelerates the efficiency of the research process. These studies have garnered national and international recognition and have now resulted in funding of both an NIH R21 and R01 grant for which the Center Director is Principal Investigator. In addition, this Resource Project is responsive to any FOA or RFA requesting studies of disease natural history such as the Natural History Studies for Rare Disease Product Development: Orphan Products Research Project Grant (R01), sponsored by the Food and Drug Administration. These instances demonstrate that in the long term, this Resource Development Project will be a sustainable, fundable research tool available to the research community.